Lung cancer contains cyclooxygenase (COX), an enzyme which metabolizes arachidonic acid to prostaglandins (PG). COX inhibitors, such as aspirin, prevent colon carcinogenesis. Here the effect of COX inhibitors were investigated on lung carcinogenesis. A/J mice were treated with carcinogens such as urethane. After 2 days, the animals were treated with COX inhibitors such as aspirin (2 mg/day s.c.) or indomethacin (5 ug/day i.o.). After 4 months, the number of lung adenomas was reduced approximately 40% by COX inhibitors. Currently, mouse lungs are being assayed for biomarkers such as cyclooxygenase using immunocytochemical as well as in situ PCR techniques. The effects of COX inhibitors were investigated on non-small cell lung cancer (NSCLC) cells. COX-2 mRNA was present in NCI-H157 cells. Phorbol esters, which activate protein kinase C, and EGF, which activates tyrosine kinase receptors, increased COX-2 gene expression. EGF increased PGE-2 levels, whereas aspirin decreased PGE-2 levels. PGE- 2 stimulated NSCLC growth in vitro whereas aspirin, indomethacin and ibuprofen inhibited NSCLC growth. Using nude mice bearing NSCLC xenografts, aspirin as well as indomethacin slowed tumor growth. These data indicate that COX inhibitors may prevent and inhibit NSCLC.